{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:50:31Z","timestamp":1786985431839,"version":"build-2736575974"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1016\/j.bmcl.2021.128133","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T12:30:19Z","timestamp":1621859419000},"page":"128133","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Identification of aryl sulfonamides as novel and potent inhibitors of NaV1.5"],"prefix":"10.1016","volume":"45","author":[{"given":"Shaoyi","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla Y.","family":"Zenova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Hussainkhel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janette","family":"Mezeyova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J.","family":"Goodchild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lindgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainbow","family":"Kwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuldip","family":"Khakh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Sojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bichler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"J.P.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Empfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph M.","family":"Dehnhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2021.128133_b0005","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00424-009-0761-0","article-title":"Cardiac sodium channelopathies","volume":"460","author":"Amin","year":"2010","journal-title":"Pflugers Arch"},{"key":"10.1016\/j.bmcl.2021.128133_b0010","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/0092-8674(95)90359-3","article-title":"SCN5A mutations associated with an inherited cardiac arrhythmia long QT syndrome","volume":"80","author":"Wang","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.bmcl.2021.128133_b0015","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/376683a0","article-title":"Molecular mechanism for an inherited cardiac arrhythmia","volume":"376","author":"Bennett","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.bmcl.2021.128133_b0020","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1016\/j.jacc.2008.02.068","article-title":"Long QT syndrome","volume":"51","author":"Goldenberg","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.bmcl.2021.128133_b0025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2010.05.011","article-title":"Molecular genetics of long QT syndrome","volume":"101","author":"Bokil","year":"2010","journal-title":"Mol Genet Metab"},{"key":"10.1016\/j.bmcl.2021.128133_b0030","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1002\/humu.21066","article-title":"The genetic basis of Brugada syndrome: a mutation update","volume":"30","author":"Hedley","year":"2009","journal-title":"Hum Mutat"},{"key":"10.1016\/j.bmcl.2021.128133_b0035","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1172\/JCI200318062","article-title":"Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)","volume":"112","author":"Benson","year":"2003","journal-title":"J Clin Invest."},{"key":"10.1016\/j.bmcl.2021.128133_b0040","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1161\/01.RES.0000050585.07097.D7","article-title":"A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill","volume":"92","author":"Groenewegen","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.bmcl.2021.128133_b0045","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/12618","article-title":"Cardiac conduction defects associate with mutations in SCN5A","volume":"23","author":"Schott","year":"1999","journal-title":"Nat Genet"},{"key":"10.1016\/j.bmcl.2021.128133_b0050","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1001\/jama.293.4.447","article-title":"Sodium channel mutations and susceptibility to heart failure and atrial fibrillation","volume":"293","author":"Olson","year":"2005","journal-title":"JAMA"},{"key":"10.1016\/j.bmcl.2021.128133_b0055","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.hrthm.2007.09.015","article-title":"Cardiac sodium channel mutation in atrial fibrillation","volume":"5","author":"Ellinor","year":"2008","journal-title":"Heart Rhythm."},{"key":"10.1016\/j.bmcl.2021.128133_b0060","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCEP.108.791434","article-title":"Dilated cardiomyopathy due to sodium channel dysfunction, what is the connection?","volume":"1","author":"Bezzina","year":"2008","journal-title":"Circ Arrhythm Electrophysiol."},{"key":"10.1016\/j.bmcl.2021.128133_b0065","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/978-3-642-41588-3_7","article-title":"The role of late INa in development of cardiac arrhythmias","volume":"221","author":"Antzelevitch","year":"2014","journal-title":"Handb Exp Pharmacol"},{"key":"10.1016\/j.bmcl.2021.128133_b0070","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/j.1875-9114.1986.tb03442.x","article-title":"Pharmacology and clinical use of mexiletine","volume":"6","author":"Fenster","year":"1986","journal-title":"Pharmacotherapy"},{"key":"10.1016\/j.bmcl.2021.128133_b0075","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1161\/01.CIR.0000139333.83620.5D","article-title":"Electrophysiologic effects of ranolazine: a novel anti-anginal agent with antiarrhythmic properties","volume":"110","author":"Antzelevitch","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.bmcl.2021.128133_b0080","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.hrthm.2011.03.045","article-title":"Electrophysiological basis for the antiarrhythmic actions of ranolazine","volume":"8","author":"Antzelevitch","year":"2011","journal-title":"Heart Rhythm."},{"key":"10.1016\/j.bmcl.2021.128133_b0085","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1016\/j.bmcl.2016.03.101","article-title":"Discovery of triazolopyridine GS-458967, a late sodium current inhibitor (late INai) of the cardiac NaV1.5 channel with improved efficacy and potency relative to ranolazine","volume":"26","author":"Koltun","year":"2016","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2021.128133_b0090","doi-asserted-by":"crossref","first-page":"9005","DOI":"10.1021\/acs.jmedchem.6b00939","article-title":"Discovery of dihydrobenzoxazepinone (GS-6615) late sodium current inhibitor (late INai), a phase II agent with demonstrated preclinical anti-Ischemic and antiarrhythmic properties","volume":"59","author":"Zablocki","year":"2016","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2021.128133_b0095","unstructured":"The hydroboration-oxidation method worked well for unsubstituted phenyl substrate tert-butyl 5-phenyl-3,6-dihydropyridine-1(2H)-carboxylate and provided tert-butyl trans-4-hydroxy-3-phenylpiperidine-1-carboxylate in 51% yield, which was used in the synthesis of analogs rac-5 \u2013 rac-28."},{"key":"10.1016\/j.bmcl.2021.128133_b0100","unstructured":"Pero JE, Lehman HDGF, Kelly MJ III, et al. Benzoxazolinone compounds with selective activity in voltage-gated sodium channels. PCT Int. Appl. WO 2014066490 A1, May 1, 2014."},{"key":"10.1016\/j.bmcl.2021.128133_b0105","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1021\/acs.jmedchem.1c00049","article-title":"Discovery of acyl-sulfonamide Nav1.7 Inhibitors GDC-0276 and GDC-0310","volume":"64","author":"Safina","year":"2021","journal-title":"J Med Chem"},{"issue":"13","key":"10.1016\/j.bmcl.2021.128133_b0110","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1161\/CIRCULATIONAHA.105.539072","article-title":"Impaired impulse propagation in Scn5a-knockout mice: combined contribution of excitability, connexin expression, and tissue architecture in relation to aging","volume":"112","author":"van Veen","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.bmcl.2021.128133_b0115","doi-asserted-by":"crossref","unstructured":"Belardinelli L, Shryock J C, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006;92(Suppl IV):iv6\u2013iv14.","DOI":"10.1136\/hrt.2005.078790"},{"key":"10.1016\/j.bmcl.2021.128133_b0120","doi-asserted-by":"crossref","first-page":"E2724","DOI":"10.1073\/pnas.1220844110","article-title":"Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels","volume":"110","author":"McCormack","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bmcl.2021.128133_b0125","unstructured":"Ahuja S, Mukund S, Deng L, et al. Structural basis of NaV1.7 inhibition by an isoform-selective small-molecule antagonist. Science. 2015;350:aac5464."},{"issue":"3","key":"10.1016\/j.bmcl.2021.128133_b0130","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1124\/mol.107.041046","article-title":"Inhibition of sodium channel gating by trapping the domain II voltage sensor with protoxin II","volume":"73","author":"Sokolov","year":"2008","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bmcl.2021.128133_b0135","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/sj.bjp.0706709","article-title":"Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action","volume":"148","author":"Fredj","year":"2006","journal-title":"Br J Pharmacol"},{"issue":"3","key":"10.1016\/j.bmcl.2021.128133_b0140","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2174\/1874467211003030129","article-title":"The enigmatic drug binding site for sodium channel inhibitors","volume":"3","author":"Mike","year":"2010","journal-title":"Curr Mol Pharm"},{"issue":"50","key":"10.1016\/j.bmcl.2021.128133_b0145","doi-asserted-by":"crossref","first-page":"14693","DOI":"10.1021\/bi7018207","article-title":"Characterization of a new class of potent inhibitors of the voltage-gated sodium channel NaV1.7","volume":"46","author":"Williams","year":"2007","journal-title":"Biochemistry"},{"issue":"5","key":"10.1016\/j.bmcl.2021.128133_b0150","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1021\/cr0306945","article-title":"Chromium- and Manganese-salen promoted epoxidation of alkenes","volume":"105","author":"McGarrigle","year":"2005","journal-title":"Chem Rev"}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X21003590?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X21003590?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:40:48Z","timestamp":1760773248000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X21003590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":30,"alternative-id":["S0960894X21003590"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2021.128133","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of aryl sulfonamides as novel and potent inhibitors of NaV1.5","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2021.128133","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"128133"}}